Nuclear acting cellular proto-oncogene DNA status and mRNA expression has been characterized in large number of lung cancer cell lines. These include c-myc, N-myc, L-myc, and p53. A variety of DNA changes have been found including amplication and gene rearrangements. A complex pattern of expression has been found with high levels of expression seen without gene amplification. The structure of the L-myc proto-oncogene, first described by our Branch has been worked out including the nucleotide sequence of the normal genomic L-myc gene as well as the cDNA sequence. This has led to the identification of a complex pattern of alternative mRNA splicing leading to a variety of L-myc mRNAs. The proteins coded for by the L-myc gene have been identified and partially characterized. The 3p(14-23) deletion first found cytogenetically has been shown to be a true DNA deletion by restriction fragment length polymorphism analysis. This has been seen in both small cell and non-small cell lung cancer making it the most frequent deletion in a common solid tumor. A series of peptides produced by lung cancer cells including insulin-like and transferrin-like growth factors, and opioid peptides have been identified as being new candidates for autocrine growth factors in the pathogenesis of lung cancer.